1. HIV Update Dr Hugh Mc Gann Consultant in Infectious Diseases
Leeds Teaching Hospitals

2. HIV 3 Things Every Respiratory Trainee Needs to Know
Dr Hugh Mc Gann
Consultant in Infectious Diseases
Leeds Teaching Hospitals

3. Globally, 34.0 million people living with HIV in 2011
Including 3.3 million children less than 15 years
2.5 millions new infections (including children); % less than in 2001
1.7 million people died of AIDS in 2011
Each day almost people newly infected
Each day more people on antiretroviral therapy

4. Adults and children estimated to be living with HIV  2011
Western &
Central Europe
[ – 1.0 million]
Eastern Europe & Central Asia
1.4 million
[1.1 million – 1.8 million]
North America
1.4 million
[1.1 million – 2.0 million]
East Asia
[ – 1.2 million]
Middle East & North Africa
[ – ]
Caribbean
[ – ]
South & South-East Asia
4.0 million
[3.1 million – 5.2 million]
Sub-Saharan Africa
23.5 million
[22.1 million – 24.8 million]
Latin America
1.4 million
[1.1 million – 1.7 million]
Oceania
53 000
[ – ]
Total: 34.0 million [31.4 million – 35.9 million]

5. Number of people newly diagnosed and people living with diagnosed HIV infection: United Kingdom,
With the transformation of HIV from a fatal to chronic life-long infection due to effective antiretroviral therapy in the mid-1990s, the number of people living with diagnosed HIV has increased year on year. with an increase in number of new diagnoses among men who have sex with men (MSM) and people born in high prevalence countries.
In 2011, there was a total of 73,660 people living with diagnosed HIV infection and 6,280 new HIV diagnoses in the UK. 5

6. New HIV diagnoses by exposure group: United Kingdom, 2002 – 20111
After adjusting for missing risk information, HIV infections acquired through heterosexual contact have accounted for 2,990 (48%) of all diagnoses in 2011.
Among MSM, the number of new HIV diagnoses have surpassed those made among heterosexuals for the first time since 1999, accounting for 3010 (48%) of all new diagnoses made in 2011.
Infections acquired through injecting drugs and through other routes have remained low over time, accounting for 140 new diagnoses each in 2011. 6

7. Late diagnosis1 of HIV infection by exposure group: United Kingdom, 2011
Late diagnosis is the most important predictor of morbidity and mortality among those with HIV infection.
In 2011, 47% (2,950) of HIV diagnoses were made at a late stage of infection (with a CD4 cell count <350 cells/mm3 within three months of diagnosis) including 26% (1,630) who were severely immunocompromised at diagnosis (CD4 cell count <200 cells/mm3).
The proportion diagnosed late was lowest among MSM (35%; 1,050), while 56% of heterosexual women (941) and 64% of heterosexual men (840) were diagnosed late.
Late diagnosis was highest among black African men (65%; 460/700) and black African women (61%; 650/1070), followed by black Caribbean women (46%; 30/60) and black Caribbean men (42%; 40/100), and white women (42%; 160/370) and white men (41%; 1,210/2960). 7

8. Case History
32 year old white British lady presented with 8 weeks of increasing breathlessness. Eventually chair bound due to dysponea
Long term partner, 2 children
GP treated with 2 courses of antibiotics and steroids but no improvement. Arranged XR with showed bilateral infiltrates – referred to chst clinic

9. Case History 2004 – Unexplained lymphadenopathy – biopsy 2006- ITP
2008 – CIN 1
2009 – trated for oro-pharyngeal candidiasis

10. Case History Admitted with severe type 2 respiratory failure
Treated for community acquired pneumonia
4 days after admission much worse

12. Case History HIV test. CD4 2 Pneumocystis pneumonia
3 week stay on ITU but recovered
Now very well CD4 546

13. Don’t Forget to Test for HIV!

14. Who to test for HIV ?
All patients where HIV including primary infection enters the differential diagnosis
Clinical indicator conditions
All acute general medical admissions where the prevalence in the local population exceeds 2/1000
Those from a country with a prevalence >1%
Men with a history of sex with other men
Injecting drug users

15. Why to test ?
100,000 people in the UK with HIV infection
25% undiagnosed with on-going transmission

16. Why to test ?
Of deaths occurring in HIV positive adults in the UK, about a quarter were directly attributable to the diagnosis of HIV being made too late for effective treatment

19. 58% had a “missed opportunity” within primary or secondary care
CD4
58% had a “missed opportunity” within primary or secondary care

20. HPTN 052 Prevention Conclusion
Early ART that suppresses viral replication led to 96% reduction of sexual transmission of HIV-1 in serodiscordant couples

21. How to test? Brief pre test explanation of rationale for the test
We use 4th generation test - HIV antibody/antigen test
Ensure all patients with positive tests are referred promptly to a HIV specialist
If a patient lacks capacity, test should be done if in “best interest”

22. HIV POCT

23. Natural history of HIV infection

24. When to treat AIDS defining illness (except TB) CD4 count < 350
CD in patients with HBV, HCV co-infection and
The trend is to start treatment earlier
Reduce non Aids morbidity/mortality
Increased risk of resistance/long term toxicity
Europe CD4 <500
US any patient regardless of CD4 count should be considered for therapy
As prevention

25. Combination anti retroviral therapy (c-ART)
Goal of therapy
Clinical
Virological
Start with 2 NRTI + NNRTI or PI
Adherence

26. NRTIs
Lamivudine
Abacavir
Zidovudine
Tenofovir

27. Non Nucleoside RTIs
Efavirenz
Nevirapine
Etravirine
Rilpivirine

28. Protease Inhibitors Lopinavir Atazanavir Darunavir
Ritonavir – used to boost levels of other PIs = Boosted PIs

29. New classes Fusion inhibitors CCR5 antagonists Integrase inhibitors
Enfuvitide (T20)
CCR5 antagonists
Maraviroc
Integrase inhibitors
Raltegravir

30. NNRTI regimes
Atripla
Truvada/Efavirenz
Eviplera
Kivexa/Efavirenz

31. PI Regimes
Truvada/Rit/Darunavir
Truvada/Rit/Atazanavir

33. HIV Prognosis
HIV is now a treatable medical condition and the majority of those living with the virus remain fit and well on treatment.
The prognosis in patients diagnosed early with good adherence is likely to be similar to a HIV negative individual
Long term c-ART may be associated with toxicity

34. HIV Drug Resistance Testing for resistance Transmitted drug resistance
Treatment failure due to resistance
Multi drug resistance in HIV

35. Long term issues Cardiovascular Bone Hepatic Renal Cancer
Increased risk of MI with HIV and with certain ARVs, Insulin resistance, dyslipidaemia
Bone
Increased risk of osteoporosis
Hepatic
Steato-hepatitis related to ARVs
Renal
Cancer

36. AIDS defining malignanciesKS
Cervical cancer
NHL
Burkitt lymphoma
Diffuse large B cell lymphoma
Primary effusion lymphoma
Plasmablastic lymphoma
Primary cerebral lymphoma

37. Non AIDS defining malignancies
Anal cancer
Hodgkin lymphoma
Other NADM (lung, germ cell, liver)

38. Facial lipoatrophy
Lipodystrophy

39. In treated patients who achieve durable suppression of the HIV virus, natural ageing, drug specific toxicity, lifestyle factors, persistent inflammation, and perhaps residual immunodeficiency are causally associated with premature development of many complications normally associated with ageing, including cardiovascular disease, cancer, and osteoporosis or osteopenia
Deeks, S. G et al. BMJ 2009;338:a3172
Copyright ©2009 BMJ Publishing Group Ltd.

40. Case History 38 Year old male asylum seeker from DRC
Right leg swelling - ?DVT
Multiple skin nodules/plaques in right groin and extensive lymphadenopathy
Biopsy – kaposi sarcoma
HIV positive – Cd4 8

41. Case History Refused to accept HIV diagnosis or take ARVs
Defaulted from follow up but represented with dysponea and back pain
KS with multiple metastaes
Treated with chemotherapy (liposomal doxyrubicin) and ARVs with significant improvement

42. Case History Discharged but stopped ARVs
3 months later re-admitted critically ill and once again treated with chemothrapy with good response
Unable to accept HIV diagnosis and take ARVs – deteriorated and admitted St Gemmas hospice for palliative care

43. Summary
HIV is a chronic condition which if diagnosed and treated early has a good long term prognosis
Health care workers should have a low threshold for HIV testing and in many situations this should be offered as an opt out service
There remains considerable stigma associated with HIV

44. Summary
In the UK Aids related deaths seen mainly in patients who present late with OIs, those unable to accept the diagnosis or adhere to ARVs and those with cancer.
HIV +ve patients may be at increased risk of cancer, toxicities of long term treatment and even premature ageing

45. Questions?